Comparison of bottom-up protein identification methods

With the rapid development of proteomics, a number of different methods appeared for the basic task of protein identification. We made a simple comparison between a common liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflow using an ion trap mass spectrometer and a combined LC-MS and LC-MS/MS method using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry and accurate peptide masses. To compare the two methods for protein identification, we grew and extracted proteins from E. coli using established protocols. Cystines were reduced and alkylated, and proteins digested by trypsin. The resulting peptide mixtures were separated by reversed-phase liquid chromatography using a 4 h gradient from 0 to 50% acetonitrile over a C18 reversed-phase column. The LC separation was coupled on-line to either a Bruker Esquire HCT ion trap or a Bruker 7 tesla APEX-Qe Qh-FTICR hybrid mass spectrometer. Data-dependent Qh-FTICR-MS/MS spectra were acquired using the quadrupole mass filter and collisionally induced dissociation into the external hexapole trap. Proteins were in both schemes identified by Mascot MS/MS ion searches and the peptides identified from these proteins in the FTICR MS/MS data were used for automatic internal calibration of the FTICR-MS data, together with ambient polydimethylcyclosiloxane ions.

Classifying monetary economics: fields and methods from past to future

We propose a simple, yet sufficiently encompassing, classification scheme of monetary economics. It comprises three fundamental fields and six recent areas that expand within and across these fields. The elements of our scheme are not found together and in their mutual relationships in earlier studies of the relevant literature; neither does this attempt aim to produce a relatively complete systematization. Our intention in taking stock is not finality or exhaustiveness. We rather suggest a viewpoint and a possible ordering of the accumulating knowledge. Our purpose is to promote discussion on the evolving nature and internal consistency of monetary economics at large.

A simple, coherent framework for partitioning uncertainty in climate predictions

A simple and coherent framework for partitioning uncertainty in multi-model climate ensembles is presented. The analysis of variance (ANOVA) is used to decompose a measure of total variation additively into scenario uncertainty, model uncertainty and internal variability. This approach requires fewer assumptions than existing methods and can be easily used to quantify uncertainty related to model-scenario interaction - the contribution to model uncertainty arising from the variation across scenarios of model deviations from the ensemble mean. Uncertainty in global mean surface air temperature is quantified as a function of lead time for a subset of the Coupled Model Intercomparison Project phase 3 ensemble and results largely agree with those published by other authors: scenario uncertainty dominates beyond 2050 and internal variability remains approximately constant over the 21st century. Both elements of model uncertainty, due to scenario-independent and scenario-dependent deviations from the ensemble mean, are found to increase with time. Estimates of model deviations that arise as by-products of the framework reveal significant differences between models that could lead to a deeper understanding of the sources of uncertainty in multi-model ensembles. For example, three models are shown diverging pattern over the 21st century, while another model exhibits an unusually large variation among its scenario-dependent deviations.

Learning in neural networks and stochastic approximation methods with averaging

The problem of adjusting the weights (learning) in multilayer feedforward neural networks (NN) is known to be of a high importance when utilizing NN techniques in various practical applications. The learning procedure is to be performed as fast as possible and in a simple computational fashion, the two requirements which are usually not satisfied practically by the methods developed so far. Moreover, the presence of random inaccuracies are usually not taken into account. In view of these three issues, an alternative stochastic approximation approach discussed in the paper, seems to be very promising.

PINCER trial: a cluster randomised trial comparing the effectiveness and cost-effectiveness of a pharmacist-led IT-based intervention with simple feedback in reducing rates of clinically important errors in medicines management in general practices

Background: Medication errors in general practice are an important source of potentially preventable morbidity and mortality. Building on previous descriptive, qualitative and pilot work, we sought to investigate the effectiveness, cost-effectiveness and likely generalisability of a complex pharm acist-led IT-based intervention aiming to improve prescribing safety in general practice. Objectives: We sought to: • Test the hypothesis that a pharmacist-led IT-based complex intervention using educational outreach and practical support is more effective than simple feedback in reducing the proportion of patients at risk from errors in prescribing and medicines management in general practice. • Conduct an economic evaluation of the cost per error avoided, from the perspective of the National Health Service (NHS). • Analyse data recorded by pharmacists, summarising the proportions of patients judged to be at clinical risk, the actions recommended by pharmacists, and actions completed in the practices. • Explore the views and experiences of healthcare professionals and NHS managers concerning the intervention; investigate potential explanations for the observed effects, and inform decisions on the future roll-out of the pharmacist-led intervention • Examine secular trends in the outcome measures of interest allowing for informal comparison between trial practices and practices that did not participate in the trial contributing to the QRESEARCH database. Methods Two-arm cluster randomised controlled trial of 72 English general practices with embedded economic analysis and longitudinal descriptive and qualitative analysis. Informal comparison of the trial findings with a national descriptive study investigating secular trends undertaken using data from practices contributing to the QRESEARCH database. The main outcomes of interest were prescribing errors and medication monitoring errors at six- and 12-months following the intervention. Results: Participants in the pharmacist intervention arm practices were significantly less likely to have been prescribed a non-selective NSAID without a proton pump inhibitor (PPI) if they had a history of peptic ulcer (OR 0.58, 95%CI 0.38, 0.89), to have been prescribed a beta-blocker if they had asthma (OR 0.73, 95% CI 0.58, 0.91) or (in those aged 75 years and older) to have been prescribed an ACE inhibitor or diuretic without a measurement of urea and electrolytes in the last 15 months (OR 0.51, 95% CI 0.34, 0.78). The economic analysis suggests that the PINCER pharmacist intervention has 95% probability of being cost effective if the decision-maker’s ceiling willingness to pay reaches £75 (6 months) or £85 (12 months) per error avoided. The intervention addressed an issue that was important to professionals and their teams and was delivered in a way that was acceptable to practices with minimum disruption of normal work processes. Comparison of the trial findings with changes seen in QRESEARCH practices indicated that any reductions achieved in the simple feedback arm were likely, in the main, to have been related to secular trends rather than the intervention. Conclusions Compared with simple feedback, the pharmacist-led intervention resulted in reductions in proportions of patients at risk of prescribing and monitoring errors for the primary outcome measures and the composite secondary outcome measures at six-months and (with the exception of the NSAID/peptic ulcer outcome measure) 12-months post-intervention. The intervention is acceptable to pharmacists and practices, and is likely to be seen as costeffective by decision makers.

Simple solution for a complex problem: Proanthocyanidins, galloyl glucoses and ellagitannins fit on a single calibration curve in high performance-gel permeation chromatography

This study was undertaken to explore gel permeation chromatography (GPC) for estimating molecular weights of proanthocyanidin fractions isolated from sainfoin (Onobrychis viciifolia). The results were compared with data obtained by thiolytic degradation of the same fractions. Polystyrene, polyethylene glycol and polymethyl methacrylate standards were not suitable for estimating the molecular weights of underivatized proanthocyanidins. Therefore, a novel HPLC-GPC method was developed based on two serially connected PolarGel-L columns using DMF that contained 5% water, 1% acetic acid and 0.15 M LiBr at 0.7 ml/min and 50 degrees C. This yielded a single calibration curve for galloyl glucoses (trigalloyl glucose, pentagalloyl glucose), ellagitannins (pedunculagin, vescalagin, punicalagin, oenothein B, gemin A), proanthocyanidins (procyanidin B2, cinnamtannin B1), and several other polyphenols (catechin, epicatechin gallate, epicallocatechin gallate, amentoflavone). These GPC predicted molecular weights represented a considerable advance over previously reported HPLC-GPC methods for underivatized proanthocyanidins. (C) 2011 Elsevier B.V. All rights reserved.

A simple analysis of thermodynamic properties for classical plasmas: I. theory

By eliminating the short range negative divergence of the Debye–Hückel pair distribution function, but retaining the exponential charge screening known to operate at large interparticle separation, the thermodynamic properties of one-component plasmas of point ions or charged hard spheres can be well represented even in the strong coupling regime. Predicted electrostatic free energies agree within 5% of simulation data for typical Coulomb interactions up to a factor of 10 times the average kinetic energy. Here, this idea is extended to the general case of a uniform ionic mixture, comprising an arbitrary number of components, embedded in a rigid neutralizing background. The new theory is implemented in two ways: (i) by an unambiguous iterative algorithm that requires numerical methods and breaks the symmetry of cross correlation functions; and (ii) by invoking generalized matrix inverses that maintain symmetry and yield completely analytic solutions, but which are not uniquely determined. The extreme computational simplicity of the theory is attractive when considering applications to complex inhomogeneous fluids of charged particles.

Bifurcation Analysis of Eigenstructure Assignment Control in a Simple Nonlinear Aircraft Model

Aircraft systems are highly nonlinear and time varying. High-performance aircraft at high angles of incidence experience undesired coupling of the lateral and longitudinal variables, resulting in departure from normal controlled � ight. The construction of a robust closed-loop control that extends the stable and decoupled � ight envelope as far as possible is pursued. For the study of these systems, nonlinear analysis methods are needed. Previously, bifurcation techniques have been used mainly to analyze open-loop nonlinear aircraft models and to investigate control effects on dynamic behavior. Linear feedback control designs constructed by eigenstructure assignment methods at a � xed � ight condition are investigated for a simple nonlinear aircraft model. Bifurcation analysis, in conjunction with linear control design methods, is shown to aid control law design for the nonlinear system.

Closed loop design for a simple nonlinear aircraft model using eigenstructure assignment

Aircraft systems are highly nonlinear and time varying. High-performance aircraft at high angles of incidence experience undesired coupling of the lateral and longitudinal variables, resulting in departure from normal controlled flight. The aim of this work is to construct a robust closed-loop control that optimally extends the stable and decoupled flight envelope. For the study of these systems nonlinear analysis methods are needed. Previously, bifurcation techniques have been used mainly to analyze open-loop nonlinear aircraft models and investigate control effects on dynamic behavior. In this work linear feedback control designs calculated by eigenstructure assignment methods are investigated for a simple aircraft model at a fixed flight condition. Bifurcation analysis in conjunction with linear control design methods is shown to aid control law design for the nonlinear system.

Downscaling from GCM precipitation: a benchmark for dynamical and statistical downscaling methods

A precipitation downscaling method is presented using precipitation from a general circulation model (GCM) as predictor. The method extends a previous method from monthly to daily temporal resolution. The simplest form of the method corrects for biases in wet-day frequency and intensity. A more sophisticated variant also takes account of flow-dependent biases in the GCM. The method is flexible and simple to implement. It is proposed here as a correction of GCM output for applications where sophisticated methods are not available, or as a benchmark for the evaluation of other downscaling methods. Applied to output from reanalyses (ECMWF, NCEP) in the region of the European Alps, the method is capable of reducing large biases in the precipitation frequency distribution, even for high quantiles. The two variants exhibit similar performances, but the ideal choice of method can depend on the GCM/reanalysis and it is recommended to test the methods in each case. Limitations of the method are found in small areas with unresolved topographic detail that influence higher-order statistics (e.g. high quantiles). When used as benchmark for three regional climate models (RCMs), the corrected reanalysis and the RCMs perform similarly in many regions, but the added value of the latter is evident for high quantiles in some small regions.

Estimating the volume of tephra deposits: a new simple strategy

Volume determination of tephra deposits is necessary for the assessment of the dynamics and hazards of explosive volcanoes. Several methods have been proposed during the past 40 years that include the analysis of crystal concentration of large pumices, integrations of various thinning relationships, and the inversion of field observations using analytical and computational models. Regardless of their strong dependence on tephra-deposit exposure and distribution of isomass/isopach contours, empirical integrations of deposit thinning trends still represent the most widely adopted strategy due to their practical and fast application. The most recent methods involve the best fitting of thinning data using various exponential seg- ments or a power-law curve on semilog plots of thickness (or mass/area) versus square root of isopach area. The exponential method is mainly sensitive to the number and the choice of straight segments, whereas the power-law method can better reproduce the natural thinning of tephra deposits but is strongly sensitive to the proximal or distal extreme of integration. We analyze a large data set of tephra deposits and propose a new empirical method for the deter- mination of tephra-deposit volumes that is based on the integration of the Weibull function. The new method shows a better agreement with observed data, reconciling the debate on the use of the exponential versus power-law method. In fact, the Weibull best fitting only depends on three free parameters, can well reproduce the gradual thinning of tephra deposits, and does not depend on the choice of arbitrary segments or of arbitrary extremes of integration.

Measuring variation in potato roots in both field and glasshouse: the search for useful yield predictors and a simple screen for root traits

Aims Potatoes have an inadequate rooting system for efficient acquisition of water and minerals and use disproportionate amounts of irrigation and fertilizer. This research determines whether significant variation in rooting characteristics of potato exists, which characters correlate with final yield and whether a simple screen for rooting traits could be developed. Methods Twenty-eight genotypes of Solanum tuberosum groups Tuberosum and Phureja were grown in the field; eight replicate blocks to final harvest, while entire root systems were excavated from four blocks. Root classes were categorised and measured. The same measurements were made on these genotypes in the glasshouse, 2 weeks post emergence. Results In the field, total root length varied from 40 m to 112 m per plant. Final yield was correlated negatively with basal root specific root length and weakly but positively with total root weight. Solanum tuberosum group Phureja genotypes had more numerous roots and proportionally more basal than stolon roots compared with Solanum tuberosum, group Tuberosum genotypes. There were significant correlations between glasshouse and field measurements. Conclusions Our data demonstrate that variability in rooting traits amongst commercially available potato genotypes exists and a robust glasshouse screen has been developed. By measuring potato roots as described in this study, it is now possible to assess rooting traits of large populations of potato genotypes.

Methods of sensory augmentation through electro-tactile stimulation of the tongue

This paper details an investigation into sensory substitution by means of direct electrical stimulation of the tongue for the purpose of information input to the human brain. In particular, a device has been constructed and a series of trials have been performed in order to demonstrate the efficacy and performance of an electro-tactile array mounted onto the tongue surface for the purpose of sensory augmentation. Tests have shown that by using a low resolution array a computer-human feedback loop can be successfully implemented by humans in order to complete tasks such as object tracking, surface shape identification and shape recognition with no training or prior experience with the device. Comparisons of this technique have been made with visual alternatives and these show that the tongue based tactile array can match such methods in convenience and accuracy in performing simple tasks.

Two fast radiative transfer methods to improve the temporal sampling of clouds in numerical weather prediction and climate models

The high computational cost of calculating the radiative heating rates in numerical weather prediction (NWP) and climate models requires that calculations are made infrequently, leading to poor sampling of the fast-changing cloud field and a poor representation of the feedback that would occur. This paper presents two related schemes for improving the temporal sampling of the cloud field. Firstly, the ‘split time-stepping’ scheme takes advantage of the independent nature of the monochromatic calculations of the ‘correlated-k’ method to split the calculation into gaseous absorption terms that are highly dependent on changes in cloud (the optically thin terms) and those that are not (optically thick). The small number of optically thin terms can then be calculated more often to capture changes in the grey absorption and scattering associated with cloud droplets and ice crystals. Secondly, the ‘incremental time-stepping’ scheme uses a simple radiative transfer calculation using only one or two monochromatic calculations representing the optically thin part of the atmospheric spectrum. These are found to be sufficient to represent the heating rate increments caused by changes in the cloud field, which can then be added to the last full calculation of the radiation code. We test these schemes in an operational forecast model configuration and find a significant improvement is achieved, for a small computational cost, over the current scheme employed at the Met Office. The ‘incremental time-stepping’ scheme is recommended for operational use, along with a new scheme to correct the surface fluxes for the change in solar zenith angle between radiation calculations.

Sparse space-time boundary element methods for the heat equation

The goal of this work is the efficient solution of the heat equation with Dirichlet or Neumann boundary conditions using the Boundary Elements Method (BEM). Efficiently solving the heat equation is useful, as it is a simple model problem for other types of parabolic problems. In complicated spatial domains as often found in engineering, BEM can be beneficial since only the boundary of the domain has to be discretised. This makes BEM easier than domain methods such as finite elements and finite differences, conventionally combined with time-stepping schemes to solve this problem. The contribution of this work is to further decrease the complexity of solving the heat equation, leading both to speed gains (in CPU time) as well as requiring smaller amounts of memory to solve the same problem. To do this we will combine the complexity gains of boundary reduction by integral equation formulations with a discretisation using wavelet bases. This reduces the total work to O(h